Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Global spatiotemporal consistency between meteorological and soil moisture drought indices

International audienc

X-rays, γ-rays and Proton Beam Monitoring with Multimode Nitrogen-doped Optical Fiber

International audienceWe investigated the potential of a multimode (50 μ m core diameter) nitrogen doped silica-based optical fiber for X-rays, protons and γ-rays radiation detection and dosimetry. X-rays results confirm that this N-doped fiber presents a strong radioluminescence (RL) around 550 nm when exposed to radiation. The RL observed from a few cm long sample linearly depends on the dose rate at least in the 1 mGy/s to 50 Gy/s range. Low dose rate γ-ray tests demonstrate the radiation detection at dose rate as low as 40 μ Gy/s with a 2 m long fiber sample. This fiber is also associated with an optically-stimulated luminescence (OSL) when exposed to a 1064 nm laser light post-irradiation. This OSL signature provides shortly after the irradiation a precise estimation of the accumulated dose at least in the 1 Gy to 10 kGy range. Under proton exposure, we benchmarked the performances of the N-doped fiber with the ones of a conventional Markus chamber used by the TRIUMF proton-therapy team. This comparison highlights the potential of the small-size N-doped fiber to partially overcome the known limitations of commercial fiber-based dosimeters for medical applications. The obtained results are very promising for the future design of more complex spatially-resolved beam monitoring systems

A splice variant in KRT71 is associated with curly coat phenotype of Selkirk Rex cats

One of the salient features of the domestic cat is the aesthetics of its fur. The Selkirk Rex breed is defined by an autosomal dominant woolly rexoid hair (ADWH) abnormality that is characterized by tightly curled hair shafts. A genome-wide case – control association study was conducted using 9 curly coated Selkirk Rex and 29 controls, including straight-coated Selkirk Rex, British Shorthair and Persian, to localize the Selkirk autosomal dominant rexoid locus (SADRE). Although the control cats were from different breed lineages, they share recent breeding histories and were validated as controls by Bayesian clustering, multi-dimensional scaling and genomic inflation. A significant association was found on cat chromosome B4 (P(raw) = 2.87 × 10(−11)), and a unique haplotype spanning ~600 Kb was found in all the curly coated cats. Direct sequencing of four candidate genes revealed a splice site variant within the KRT71 gene associated with the hair abnormality in Selkirk Rex

Ethnic-Specific Normative Reference Values for Echocardiographic LA and LV Size, LV Mass, and Systolic Function The EchoNoRMAL Study

OBJECTIVES: This study sought to derive age-, sex-, and ethnic-appropriate adult reference values for left atrial (LA) and left ventricular (LV) dimensions and volumes, LV mass, fractional shortening, and ejection fraction (EF) derived from geographically diverse population studies. BACKGROUND: The current recommended reference values for measurements from echocardiography may not be suitable to the diverse world population to which they are now applied. METHODS: Population-based datasets of echocardiographic measurements from 22,404 adults without clinical cardiovascular or renal disease, hypertension, or diabetes were combined in an individual person data meta-analysis. Quantile regression was used to derive reference values at the 95th percentile (upper reference value [URV]) and fifth percentile (lower reference value [LRV]) of each measurement against age (treated as linear), separately within sex and ethnic groups. RESULTS: The URVs for left ventricular end-diastolic volume (LVEDV), LV end-systolic volume, and LV stroke volume (SV) were highest in Europeans and lowest in South Asians. Important sex and ethnic differences remained after indexation by body surface area or height for these measurements, as well as for the LRV for SV. LVEDV and SV decreased with increasing age for all groups. Importantly, the LRV for EF differed by ethnicity; there was a clear apparent difference between Europeans and Asians. The URVs for LV end-diastolic diameter and LV end-systolic diameter were higher for Europeans than those for East Asian, South Asian, and African people, particularly among men. Similarly, the URVs for LA diameter and volume were highest for Europeans. CONCLUSIONS: Sex- and/or ethnic-appropriate echocardiographic reference values are indicated for many measurements of LA and LV size, LV mass, and EF. Reference values for LV volumes and mass also differ across the age range.status: publishe